Hydrochloric Acid → HCID 57904819, compound

To a stirred solution of 8-(chloromethyl)-1,4-dioxaspiro[4.5]decane (78 g, 409 mmol) in THF (200 mL) was added 1N aq. HCl (500 mL, 500 mmol) at room temperature. After 24 h, 30% NH4OH (106 mL, 818 mmol) followed by NaCN (22.05 g, 450 mmol) were added and stirring continued for an additional 72 h at rt. The reaction mixture was then extracted with CH2Cl2 (5×100 mL). The combined CH2Cl2 extracts were treated with Na2CO3 (50.7 g, 409 mmol) in water (200 mL) followed by benzylchloroformate (58.4 mL, 409 mmol) at 0° C. and the resulting mixture allowed to warm to room temp and stirred overnight (16 h). After this, the reaction mixture was washed with sat. NaHCO3 (200 mL), then dried (Na2SO4), filtered and concentrated to afford a yellow residue. To this residue was added 20% ethyl acetate/hexane (150 mL) and the precipitated product was triturated with hexane (500 mL) and filtered. The filter cake was washed with hexane to afford benzyl 4-(chloromethyl)-1-cyanocyclohexylcarbamate (77 g, 251 mmol, 61% yield) as a pale yellow solid. 1H NMR (500 MHz, CDCl3) δ: 7.31-7.40 (5 H, m), 5.14 (2 H, s), 4.92 (0.8 H, br.s.), 4.78 (0.2 H, br.s), 3.42 (2 H, dd, J=6.6, 2.3 Hz), 2.55-2.61 (2 H, m), 2.21-2.28 (1 H, m), 2.04 (2 H, s), 1.30-1.83 (4 H, m). LCMS (M+H) calcd for C16H20ClN2O2: 307.12; found: 307.07.

1. additionwere added
2. waitcontinued for an additional 72 h at rt
3. extractionThe reaction mixture was then extracted with CH2Cl2 (5×100 mL)
4. stirringstirred overnight (16 h)
5. washAfter this, the reaction mixture was washed with sat. NaHCO3 (200 mL)
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customto afford a yellow residue
10. customthe precipitated product was triturated with hexane (500 mL)
11. filtrationfiltered
12. washThe filter cake was washed with hexane

ORD record

ord-d5f4ef7c706b4564bc3203ed4c065220

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08129398B2